Alcohol is one of the most addictive substances on the planet, and for those who develop a dependency, sudden withdrawal can produce physical symptoms in the body such as shaking and delirium. But, while much is known about how alcohol withdrawal affects the body, a recent study delved deeper, and investigated how sudden alcohol withdrawal affects the brain.

For the study, now published in the online journal Proceedings of the National Academy of Sciences, researchers from the Zentralinstitut für Seelische Gesundheit, a center for psychiatric medicine in Germany, first examined the brains of deceased alcoholics. Initially, they observed noticeable differences in areas of the brain associated with producing and transporting dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers.

The research team found the brains of deceased alcoholics to have  fewer D1 dopamine receptors, sites in the brain where dopamine binds and excites neurons, the specialized brain cells that transmit nerve impulses. Fewer D1 receptors would make the brain less responsive to dopamine, causing an individual to struggle in order to feel the same euphoric rush from alcohol that others may experience.

The brains of deceased alcoholics also had fewer dopamine transporter sites, areas that allow for unused dopamine to be retrieved for later reuse. However, the brains weren’t lacking in D2 dopamine receptor sites, areas that bind to dopamine in order to restrain neuron excitation, IFL Science reported. According to the research, the combination of these characteristics would ultimately interfere with the brain’s ability to use dopamine, and subsequently inhibit the individual's ability to feel pleasure.

All together, the team noted that the brains of deceased alcoholics were in a hypodopaminergic state, or a state in which dopamine levels are significantly below average. This would explain why alcoholics would continue to seek more and more alcohol in order to achieve the same pleasure. In addition to addiction, dopamine deficiencies are also often associated with conditions such as depression and psychological disorders.

The team then sought to understand exactly how the alcoholic-brain ended up in such a depleted state. To do this, they tracked the dopamine levels of alcohol-dependent rats that were denied their drug for several weeks. Following the sudden withdrawal, dopamine levels in the rat brains initially dropped and receptor and transporter site numbers remained the same — such as in the brains of the deceased alcohol addicts. The hypodopaminergic state also led to hyperactivity and enhanced alcohol-seeking behavior in the animals, MedicalXpress reported. Even after three weeks of abstinence, alcoholic mice still acted in ways associated with alcohol cravings.

Eventually, after three weeks of alcohol abstinence, the number of transporter and receptor sites decreased. This change meant that there was less dopamine available to bind to the receptor sites and more left unused. This created a hyper dopaminergic state, or one where the dopamine levels are higher than normal. But while having more dopamine may sound like a good thing, according to the study both hypo and hyper dopaminergic states put abstinent drinkers at risk of relapse.

The findings help better shape our understanding of alcohol’s effect on dopamine levels and will hopefully help lead to better treatment for those with alcohol addiction.

Source: Hirth N, Meinhardt MW, Noori HR, et al. Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence. PNAS . 2016